tetano
Editor, Senior Moderator
J Biomol Struct Dyn
. 2026 Jan 26:1-12.
doi: 10.1080/07391102.2025.2609686. Online ahead of print.
Mutations in SARS-CoV-2 spike protein identified by mass spectrometry based phylogenetics and their structural and functional consequences
Matthew Wright[SUP] 1 [/SUP], Kevin M Downard[SUP] 1 [/SUP]
Affiliations
The structural and functional consequences of mutations located throughout the S1 and S2 subunit domains of spike protein among omicron and D614G-mutant originating forms of the SARS-CoV-2 virus are examined. These structural mutations were identified by a mass-based phylogenetics approach. The T95I mutation, located in the S1 N-terminal domain, and the T547K mutation of the receptor-binding domain both help to stabilise the spike protein structure and contribute to viral fitness in omicron variants. The D796Y within the N-terminal portion of the S2 subunit, also stabilises the protein, while the effects of Q954H and N969K combine to reduce infectivity through displacement of the backbone of the heptad repeat 2 (HR2) region. The N856K mutation, within the fusion peptide region, introduces a stabilising H-bond at residue T572 that both alters the S1/S2 interaction and hampers conformational change resulting in a mixed stabilisation effect.
Keywords: Mutation; SARS-CoV-2; coronavirus; mass spectrometry; spike protein; structural phylogenetics.
. 2026 Jan 26:1-12.
doi: 10.1080/07391102.2025.2609686. Online ahead of print.
Mutations in SARS-CoV-2 spike protein identified by mass spectrometry based phylogenetics and their structural and functional consequences
Matthew Wright[SUP] 1 [/SUP], Kevin M Downard[SUP] 1 [/SUP]
Affiliations
- PMID: 41587096
- DOI: 10.1080/07391102.2025.2609686
The structural and functional consequences of mutations located throughout the S1 and S2 subunit domains of spike protein among omicron and D614G-mutant originating forms of the SARS-CoV-2 virus are examined. These structural mutations were identified by a mass-based phylogenetics approach. The T95I mutation, located in the S1 N-terminal domain, and the T547K mutation of the receptor-binding domain both help to stabilise the spike protein structure and contribute to viral fitness in omicron variants. The D796Y within the N-terminal portion of the S2 subunit, also stabilises the protein, while the effects of Q954H and N969K combine to reduce infectivity through displacement of the backbone of the heptad repeat 2 (HR2) region. The N856K mutation, within the fusion peptide region, introduces a stabilising H-bond at residue T572 that both alters the S1/S2 interaction and hampers conformational change resulting in a mixed stabilisation effect.
Keywords: Mutation; SARS-CoV-2; coronavirus; mass spectrometry; spike protein; structural phylogenetics.